AB1140 TREATMENT WITH TNF AND IL17 INHIBITORS DIFFERENTLY AFFECTS SERUM LIPID PROFILE AND TH1/TH2 IMMUNE RESPONSE IN ANKYLOSING SPONDYLITIS AND PSORIATIC ARTHRITIS.
Authors: K. Bonek, S. Szczygielska, M. Kajfasz, A. Felis-Giemza, B. Kwiatkowska, M. Wisłowska, E. Kuca-Warnawin, P. Głuszko
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Psoriatic arthritis (PsA) is a form of spondyloarthritis (SpA) associated with alterations to the serum lipid profile. Current research suggests that biological treatment with TNF and IL-17 inhibitors differently affects the lipid profile and Th cells populations in PsA and ankylosing spondylitis (AS) <h3>Objectives</h3> To investigate the relationship between lipid profile, disease activity and T-cells phenotype changes in patients with SpAs treated with TNF and IL-17 inhibitors. <h3>Methods</h3> A group of 36 SpA patients (AS 14, PsA 22) with high disease activity were assessed at the start and after 6 months of anti TNF (n=19) and anti IL17 (n=17) treatment. Serum lipid profile: triglycerides (TG), total cholesterol (TC), low (LDL), and high-density lipoproteins (HDL), nonHDL, VLDL levels and atherogenic index (AI) were evaluated. Frequency of Th1, Th2, Th1/Th17, Th17 and T regulatory cells (Tregs) was determined by flow cytometry. The Spearman's rank test was used for the statistical analysis of correlations, and the Wilcoxon rank test for dependent sample testing. All data are given as medians and the absolute and relative difference between two variables are expressed as delta. <h3>Results</h3> A significant reduction in disease activity was observed in all treated patients: DAPSA (32,5 vs 4); BASDAI (6,8 vs 1,5; p&lt;0,01), ESR (15 vs 5 mm/h; p&lt;0,01) and CRP (6 vs 1 mg/l; p=0,03). In all 36 patients, the reduction of disease activity was followed by a mild decrease of TC (205 vs 195 mg/dL p&lt;0,01), LDL (120 vs 110 mg/dL p&lt;0,02) and non-HDL levels (18 vs 5 vs 12 mg/dL, p&lt;0,05). In PsA patients treated with IL-17 inhibitor (n=13) we found a statistically significant, more pronounced decrease in lipid levels compared to AS and PsA patients treated with anti-TNFs i.e: delta of TC (19 vs 12 vs 12 mg/dLp=0,03), LDL (23 vs 15 vs 10 mg/dL p&lt;0,05) and VLDL (11 vs 4 vs 4,5mg/dl p=0,02). In addition, in PsA group (n=22) after 6 months of treatment, we found reduction of TG (144 vs 94 mg/dL p=0,05), VLDL (28,8 vs 20,6 mg/dL p=0,04) levels and improvement of AI (4,4 vs 3,5 p=0,03), also deltas of DAPSA correlated positively with deltas of TC (rho=0,6 p=0,03) and nonHDL (rho=0,5 p=0,04). In flow cytometry after 6 months of treatment of all 36 patients we observed a rise of Th1 (11,3 vs 12,6% p=0,05) and a decrease of Th2 (5,7 vs 4,7% p=0,03) cells with almost no change in Treg cells (5,3 vs 5,35%). In PsA patients (n=22) we have found correlations (p&lt;0,05) between decreases of CD4+CD25+ counts and levels of TC (rho=0,6), nonHDL (rho=0,5), AI (rho=0,6) and DAPSA (rho=0,5). Effectiveness of treatment with iTNFs and iIL-17s was comparable in PsA or AS, but some differences were observed in alterations to limphocyte profile. Patients treated with anti-IL-17 (PsA 13/ AS 4) showed a more pronounced increase in the Th1/Th17-like cell percentage (9,3 vs 13,5%; p=0,04) with a decrease of Th2 cells (7,3 vs 3,5%p=0,03) and concomitant increase in Th1 cells (11 vs 13,8%). In patients treated with IL-17 inhibitors increase of Th1 cells correlated negatively (p&lt;0,05) with TG (rho=-0,6), nonHDL (rho=-0,7), LDL(rho=-0,6) levels, VLDL(rho=-0,6) and positively with HDL (rho=0,4). In PsA patients Th1 cells correlated with DAPSA (rho=-0,4). Patients treated with antiTNFs (AS 10/PsA 9) revealed an increase of Th1 cells (10,5 vs 12% p=0,04) and also a decrease of CD4+CD25+ (23 vs 14,5%; p=0,008), but no correlations with lipid profile were found. <h3>Conclusion</h3> Anti TNF and anti IL17 treatment distinctively affects lipid profile and T Cell balance especially in PsA. Patients with SpAs treated with biologics presented a tendency towards reduction of TC and LDL concentrations, but in PsA those changes were stronger with additional reduction of VLDL, non-HDL and TG levels. Alterations in the lipid profile correlate with disease activity in PsA and with a shift in Th cells (increase in the Th1/Th2 ratio with a decrease in the percentage of activated CD4+CD25+ T cells), which was not observed in AS. <h3>REFERENCES:</h3> NIL. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.